The central theme for this Program Project is "Biological and Chemical Interactions of Chemical Mixtures." Since the field of chemical mixture research is complex and still largely unexplored, the ultimate goal of this program is to incorporate state-of the-art science into human and ecological risk assessment methodologies for chemical mixtures as well as engineering remediation technology related to Superfund hazardous waste disposal sites. The various projects and cores will work in concert to attempt to: (1) determine target tissue dosimetry of chemicals under the condition of low-level, long-term exposure to chemical mixtures by coupling physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) modeling, experimental toxicology, and statistical/mathematical modeling; (2) characterize interactive hepatotoxicity and hepatocarcinogenesis of chemical mixtures related to hazardous waste disposal; (3) establish molecular biomarkers for human exposure to environmental chemical mixtures; (4) develop invertebrate bioreporters for environmental pollution through molecular biology and molecular genetics technology; (5) define ecological impacts resulting from chemical mixture exposure related to Superfund hazardous waste sites; (6) develop engineering technologies for remediation of chemical mixture contaminated water. The proposed research will encompass both laboratory work on chemically defined mixtures of high priority hazardous waste substances and field work on and related to two Superfund sites in Colorado. Ultimately, this program should make significant contributions to innovative and efficient reduction of the amount and toxicity of hazardous wastes, preventing adverse human health effects, and minimizing ecological impact. This integrated program involves 17 different disciplines or specialties from 7 academic departments in 3 colleges plus collaborative scientists from outside o Colorado State University (CSU). The Program Project consists of 3 Cores (Administrative and Training, Analytical Chemistry and molecular Biology, and Spatial Information Analysis and Statistics) and 66 research Projects which are grouped under two Emphases. Under the Biomedical/Ecological/Epidemiological Emphasis, there ar three mechanistically-based toxicology projects (Project 1, PB-PK/PD Modeling; Project 2, Hepatocarcinogenesis; Project 3, Interactive Hepatotoxicity) and two molecular biology and ecology projects; Project 5, Molecular Genetic Bioreporting; Project 6, Mechanistic Ecological Evaluation; Under the Engineering Emphasis, there is one project Project 8, Environmental Biotechnology.